The paradoxical role of the transient receptor potential vanilloid 1 receptor in inflammation.

The transient potential receptor vanilloid 1 (TRPV1) receptor is a non-selective cation channel that is chemically activated by capsaicin, the pungent component of hot peppers. In addition, endogenous compounds, in particular the endogenous cannabinoid receptor activator, anandamide, have been demonstrated to activate TRPV1 in vivo. TRPV1 receptors are also activated by temperatures within the noxious range (>43 degrees C) and low pH (<pH 6.0). TRPV1 receptors are predominantly expressed in primary afferent fibres which are peptidergic sensory neurones, such as the thinly myelinated A-delta and unmyelinated C-fibres. TRPV1 receptors have also been demonstrated to be present in non-neuronal cells. Historically, TRPV1 has been considered as a pro-inflammatory receptor due to its key role in several conditions, including neuropathic pain, joint inflammation and inflammatory bowel disease, amongst others. However, the purpose of this review is to underline the emerging new evidence which demonstrate paradoxical, protective functions for this unique receptor in vivo. For example, in experimentally induced sepsis, TRPV1 null mice demonstrated elevated levels of pathological markers in comparison to wild-type mice. In addition to the pro-inflammatory and protective roles of TRPV1 in pathophysiological states, TRPV1 has also been shown to have important functions under normal physiological conditions, for example in urinary bladder function, thermoregulation and neurogenesis. The emerging functions of TRPV1 highlight the necessity for further research in light of increasing reports of potential TRPV1 antagonists undergoing pre-clinical experimentations.